NCT02704533

Sequential Optimization of Dose and Schedule of PfSPZ Vaccine

Sequential Optimization of Dose and Schedule of PfSPZ Vaccine, Verified by Randomized, Controlled, Double-blind Immunization and Controlled Human Malaria Infection in Malaria-naïve, Healthy Adult Volunteers in Germany

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 45 (actual)
• Sponsor: Sanaria Inc. · Industry
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

MAVACHE is a sequential dose and schedule optimization trial of intravenous immunization with PfSPZ Vaccine in 18 to 54 malaria-naïve, healthy adult volunteers receiving 9x10\^5, 1.35x10\^6, or 2.7x10\^6 PfSPZ per dose and a total dose between 2.7x10\^6 and 8.1x10\^6 PfSPZ followed by CHMI with 3,200 fully infectious PfSPZ (PfSPZ Challenge). PfSPZ Challenge (7G8) to assess vaccine efficacy, safety, tolerability and infectivity of ascending PfSPZ doses will be assessed in healthy, malaria-naïve volunteers.

Detailed description

The study is to take place at Institut für Tropenmedizin, Eberhard Karls Universität Tübingen, Tübingen Germany. The study has two phases: 1) dose optimization, and 2) regimen verification. In the first phase groups A, B1, B2, C1, C2 and C3 will be vaccinated sequentially in a pre-specified order, followed by homologous CHMI with 3,200 PfSPZ Challenge (NF54) three weeks after last vaccine injection. Dose optimization phase A: 9x10\^5 PfSPZ on Days 0, 7 and 28 (n = 6) B1: 1.35x10\^6 PfSPZ on Days 0 and 7 (n = 6) B2: 1.35x10\^6 PfSPZ on Days 0, 7, and 28 (n = 6) C1: 2.7x10\^6 PfSPZ on Day 0 (n = 6) C2: 2.7x10\^6 PfSPZ on Day 0 and 7 (n = 6) C3: 2.7x10\^6 PfSPZ on Days 0, 7 and 28 (n = 6) In parallel to CHMI with PfSPZ Challenge (NF54) during the optimization phase, a total of nine volunteers will receive either 800, 1,600 or 3,200 PfSPZ Challenge (7G8) (PfSPZ Challenge (7G8) dose finding) to assess safety, tolerability and infectivity of PfSPZ Challenge (7G8) in malaria-naïve healthy adult volunteers. PfSPZ Challenge (7G8) dose finding/infection D1: 800 PfSPZ (n = 3) D2: 1,600 PfSPZ (n = 3) D3: 3,200 PfSPZ (n = 3) Subsequently, the shortest efficacious regimen (V1) and a three-dose regimen (Day 0, 7 and 28) of the highest safe dose (V2) will be selected and verified against placebo (normal saline (NS)). Groups V1 and V2 will be vaccinated at approximately the same time and undergo repeat CHMI three and eight weeks after the last immunization. Volunteers will either receive PfSPZ Vaccine or NS as placebo. Allocation will be random and double blind. Repeat CHMI will be done with PfSPZ Challenge (NF54) and PfSPZ Challenge (7G8), given in a randomized sequence. All immunizations are given by direct venous inoculation (DVI). Regimen verification phase V1: Shortest efficacious regimen (n = 12) against placebo (n = 6) V2: Maximum regimen (n = 12) against placebo (n = 6) P1: Placebo for V1 group (n=6) P2 Placebo for V2 group (n=6)

Conditions

• Malaria

Interventions

Type	Name	Description
BIOLOGICAL	PfSPZ Vaccine	Aseptic, purified, vialed, cryopreserved, radiation-attenuated, Plasmodium falciparum sporozoites, strain NF54
BIOLOGICAL	PfSPZ Challenge (NF54)	Live, infectious, aseptic, purified, vialed, cryopreserved, Plasmodium falciparum sporozoites, strain NF54
BIOLOGICAL	PfSPZ Challenge (7G8)	Live, infectious, aseptic, purified, vialed, cryopreserved, Plasmodium falciparum sporozoites, strain 7G8
OTHER	Normal saline	0.9% sodium chloride

Timeline

• Start date: 2016-08-29
• Primary completion: 2018-10-19
• Completion: 2018-12-01
• First posted: 2016-03-10
• Last updated: 2019-02-01

Locations

1 site across 1 country: Germany